title: Apoptotic markers in a prostate cancer cell line: effect of ellagic acid.
abstract: Ellagic acid (EA) inhibits cell growth and induces apoptosis in cultured cells; however, the precise molecular mechanism involved in EA-induced apoptosis in prostate cancer cells is unknown. The aim of the present study was to delineate possible apoptotic pathway(s) involved in the EA-mediated chemotherapeutic effects in the LNCaP human prostatic cancer cell line. EA produced anti-proliferative effects through inhibition of rapamycin (mTOR) activation and a reduction in intracellular levels of β-catenin. Moreover, we demonstrated that EA induced apoptosis via downregulation of the anti-apoptotic proteins, silent information regulator 1 (SIRT1), human antigen R (HuR) and heme oxygenase-1 (HO-1). EA modulated the expression of apoptosis-inducing factor (AIF) resulting in a significant increase in reactive oxygen species (ROS) levels and the activation of caspase-3. Finally, we demonstrated that EA reduced both transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) levels. EA treatment resulted in the increased expression of the tumor suppressor protein p21 and increased the percentage of apoptotic cells. In conclusion, the results suggest that EA treatment represents a new and highly effective strategy in reducing prostate cancer carcinogenesis.
authors.affiliation: Department of Drug Science, Section of Biochemistry, University of Catania, I-95125 Catania, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vanella
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Giacomo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Ignazio
authors.initials: I
authors.lastname: Barbagallo
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.forename: Valeria
authors.initials: V
authors.lastname: Sorrenti
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004610:Ellagic Acid / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D017382:Reactive Oxygen Species; D051176:beta Catenin; D004610:Ellagic Acid; D051547:Heme Oxygenase-1; D053148:Caspase 3